TB Research

<i>Mycobacterium tuberculosis</i> Rv0927c Inhibits NF-κB Pathway by Downregulating the Phosphorylation Level of IκBα and Enhances Mycobacterial Survival

Xia A, Li X, Quan J, Chen X, Xu Z, Jiao X

Frontiers in immunology · 2021-08

Abstract

Through long-term coevolution with its host, Mycobacterium tuberculosis ( M. tuberculosis ) uses multiple strategies to escape host defenses. The M. tuberculosis Rv0927c protein is predicted to be a short-chain dehydrogenase/reductase related to bacterial metabolism. However, the role of Rv0927c during M. tuberculosis infection remains unclear. Here, we observed that Rv0927c inhibited the expression of IL-6, TNF-α, and IL-1β, an effect dependent on NF-κB and p38 pathways. Western blot analysis of macrophages infected with recombinant Mycobacterium smegmatis strains showed that Rv0927c attenuated NF-κB activation by downregulating the phosphorylation of IκBα. Additionally, Rv0927c enhanced intracellular survival of M. smegmatis and pathological effects in mice. In conclusion, our findings demonstrate that Rv0927c functions as a regulator of inflammatory genes and enhances the survival of M. smegmatis .

MeSH terms

  • Macrophages
  • Animals
  • Mice
  • Mycobacterium tuberculosis
  • Tuberculosis
  • Disease Models, Animal
  • Oxidoreductases
  • Bacterial Proteins
  • NF-kappa B
  • Inflammation Mediators
  • Cytokines
  • Signal Transduction
  • Gene Expression Regulation, Bacterial
  • Phosphorylation
  • Microbial Viability
  • Host-Pathogen Interactions
  • Biomarkers
  • NF-KappaB Inhibitor alpha